Physical exercise can be used to elicit and study maximal responses of various metabolic systems. It is proposed that continuous infusion, dual labeling tracer techniques be used to study lactic acid metabolism during rest and exercise in laboratory rats. The effects of exercise intensity, ambient oxygen tension, and physical training on the rates and pathways of lactate turnover and oxidation will be studied. In each condition the production of lactate will be compared with the rate of glycolysis as estimated from the combined rates of glucose removal and skeletal muscle glycogenolysis. Continuous infusion techniques will also be used to study the turnovers of amino acids (such as leucine, alanine, glutamine, glutamate) whose metabolisms are linked to the carbon flow sustaining exercise. The pathways of lactate removal during the post-exercise (O2 debt) period will be investigated by means of kinetic tracer studies utilizing single pulse injections of (U-14C)-lactate, sampling of arterial blood, forced ventilation, and freeze clamping of skeletal muscle, liver, kidney, and heart. Metabolite pool sizes and specific activities in the various tissues over time will be determined by a variety of techniques involving two dimensional chromatgraphy, liquid scintillation counting, autoradiography, and enzymatic assays. These studies will contribute to understanding the causes, rates, controls, and pathways of lactate metabolism during and immediately after exercise. It is also proposed that the unique methodologies available be employed to address other major question of interest in exercise physiology. The hypothesis will be tested that carbohydrate derivatives such as pyruvate (and to a lesser extent, particular amino acids) play anaplerotic roles in maintaining levels of the TCA cycle intermediate OAA during exericse. In this way the temporal correlation between muscle fatigue and glycogen depletion may be explained.